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Chloroquine and hydroxychloroquine are antimalarial drugs currently being used under Emergency Use Authorization as treatments for COVID-19. Recently published data from a mouse study suggest that these drugs carry a significant risk of death when either is given in combination with metformin.

Metformin is a drug commonly used to treat type 2 diabetes. It is the fourth most commonly prescribed medication in the United States, with more than 80 million prescriptions for the drug written yearly.

Previous research has demonstrated that chloroquine and metformin, when used independently, exert anti-cancer effects. The current study investigated whether the two drugs, when used in combination, would have a synergistic effect against cancer.

The authors of the study injected mice with saline, chloroquine, hydroxychloroquine, and/or metformin for four weeks. They found that the combination of chloroquine and metformin killed 40 percent of the mice. The combination of hydroxychloroquine and metformin killed 30 to 40 percent of the mice. All the treated mice exhibited high levels of lactate dehydrogenase and creatine kinase – indicators of tissue damage. Some of the mice treated with hydroxychloroquine and metformin exhibited signs of increased autophagy in their hearts, livers, and kidneys.

These findings suggest that when chloroquine or hydroxychloroquine are given in combination with metformin, they can increase the risk of death in mice. Further clinical trials are needed to determine if these findings translate to humans.

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